The invention relates to columns used in liquid chromatography.
Liquid chromatography is a technique for separating the individual compounds that exist in a subject sample. In employing the technique, the subject sample is carried in a liquid, called a mobile phase. The mobile phase carrying the subject sample is caused to migrate through a media, sometimes called a stationary phase. Different compounds will have differing rates of migration through the media, which effects the separation of the components in the subject sample. Liquid chromatography is commonly performed with reusable columns or with disposable cartridges, both of which are usually cylindrical, in which the media bed is bounded axially by porous plates, or plates containing defined flow paths, through which the mobile phase will flow. (See U.S. Pat. No. 4,250,035 to McDonald et al.)
The present invention provides apparatus for chromatography. In general, in one aspect, the invention features a chromatography apparatus including a tubular member having an inlet end and an outlet end. The tubular member includes an innermost first layer comprised of a first material and a second layer comprised of a second material.
Embodiments of the invention may include one or more of the following. The chromatography apparatus can further include a first intermediate layer formed from a third material, where at least a portion of the first intermediate layer is disposed between the innermost first layer and the second layer. The first intermediate layer can be formed from an adhesive material. The chromatography apparatus can further include a second intermediate layer formed from a fourth material, where at least a portion of the second intermediate layer is disposed between the innermost first layer and the second layer. A portion of the second intermediate layer can be disposed between the second layer and the first intermediate layer.
The tubular member of the chromatography apparatus can include a plurality of layers, including at least the innermost first layer formed of the first material and a second layer formed of the second material. The second layer can be an intermediate layer and an outermost layer can be included, formed also of the first material. In one embodiment, the first material can encapsulate the second layer, thereby forming an outermost layer of the first material.
The outer surface of the second layer can have a cross-sectional shape having at least one flat side. For example, the outer surface can have a rectangular cross-sectional shape, or a square cross-sectional shape. In other embodiments, the outer surface can have a circular cross-sectional shape, a triangular cross-sectional shape, hexagonal cross-sectional shape or an octagonal cross-sectional shape.
The second layer can be formed from a deformable material and/or a rigid material. For example, the second layer can be formed from a polyolefin (e.g., polypropylene or polyethylene), stainless steel, aluminum, anodized aluminum, acetal, polycarbonate or glass. The innermost first layer can be formed from a chemically inert material. For example, the innermost first layer can be formed from a fluoropolymer, such as TEFLON, TEFZEL, EFEP or PTFE, and can be a lining, sleeve, or cladding. The innermost first layer may be impregnated in the second layer or may be formed by, coating, encapsulating, co-extrusion, anodizing, or bonding. Innermost first layers of TEFLON or like materials may be formed by TEFLON hardcoating or a similar technique. Forming an innermost first layer of TEFLON on an aluminum outer layer or intermediate layer surface through TEFLON hardcoating is an exemplary technique. The innermost first layer can also be formed from a deformable material and/or a rigid material. In one embodiment, the second layer can be formed from polypropylene and the innermost first layer formed from TEFLON. In another embodiment, the second layer can be formed from polyethylene and the innermost first layer formed from TEFLON.
In general, in another aspect, the invention features a chromatography column including a tubular member having an inlet and outlet end, first and second porous members disposed within the tubular member, and a chromatography or separation media disposed within the tubular member and bounded by the first and second porous members. The tubular member includes an innermost first layer formed from a chemically inert material and a second layer. The first porous member abuts the media and the first member is also in slidable contact with the inner layer of the tubular member, and is spaced sufficiently from the inlet end to define a module receiving region for receiving a sample module entirely within the tubular member.
Embodiments of the invention may include one or more of the following. The tubular member of the chromatography column can include a plurality of layers, including at least the innermost first layer (formed from the chemically inert material) and the second layer. The second layer can be an intermediate layer, and an outermost layer can be formed from the chemically inert material. In one embodiment the chemically inert material encapsulates the second layer, thereby forming both an innermost first layer and an outermost layer comprised of the chemically inert material.
The tubular member can further include a sealing region between the inlet end and the module receiving region. The sealing region is sufficiently long to receive a sealing head for making a seal with the innermost first surface of the tubular member. The tubular member can include a chamfered region near the inlet end.
The second layer of the chromatography column can be formed from polypropylene, polyethylene, stainless steel, aluminum, anodized aluminum, acetal, polycarbonate or glass. The innermost first layer of the chromatography column can be formed from a fluoropolymer, such as TEFLON, TEFZEL, EFEP or PTFE. In one embodiment, the second layer can be formed from either polypropylene or polyethylene and the innermost first layer formed from TEFLON.
In general, in another aspect, the invention features a chromatography column including a tubular member having an inlet and outlet end, first and second porous members disposed within the tubular member, and a chromatography or separating media disposed within the tubular member and bounded by the first and second porous members. The tubular member includes an innermost first layer formed from a chemically inert material and a rigid and/or deformable second layer. The second porous member abuts the media and is held firmly by crimping a portion of the tubular member against the second porous member.
Embodiments of the invention may include one or more of the following. The tubular member included in the chromatography column can include a plurality of layers, including at least the innermost first layer formed from the chemically inert material and the rigid, deformable second layer. The second layer can be an intermediate layer and an outermost layer can be formed from the chemically inert material. In one embodiment, the chemically inert material encapsulates the second layer, thereby forming both an innermost first layer and an outermost layer of the chemically inert material.
The first porous member can be in slidable contact with the innermost first layer, and spaced sufficiently from the inlet end to form a module receiving region deep enough for a sample module to be inserted completely into the receiving region.
The first porous member can be held firmly by crimping the column wall against or above the first porous member. The crimped first porous member can be spaced sufficiently from the inlet end to form a module receiving region deep enough for a sample module to be inserted completely into the receiving region. The column wall may be crimped into a grooved region of the first porous member.
The tubular member can further include a sealing region between the inlet end and the module receiving region, the sealing region being sufficiently long to receive a sealing head for making a seal with the inner surface of the tubular member. The tubular member can include a chamfered region near the inlet end.
The second layer can be formed from polypropylene, polyethylene, stainless steel, aluminum, anodized aluminum, acetal, polycarbonate or glass. The innermost first layer can be formed from a fluoropolymer, such as TEFLON, TEFZEL, EFEP or PTFE. In one embodiment the outer layer can be formed from either polypropylene or polyethylene and the innermost first layer formed from TEFLON.
The inlet end of the tubular member can include an inlet tube abutting an upper surface of the first porous member. The inlet tube can have an inner layer formed from a chemically inert material. The chemically inert material can be a fluoropolymer, such as TEFLON, TEFZEL, EFEP or PTFE. The outlet end of the tubular member can include an outlet tube abutting a lower surface of the second porous member. The outlet tube can have an inner layer comprising a chemically inert material. The chemically inert material can be a fluoropolymer, such as TEFLON, TEFZEL, EFEP or PTFE.
In general, in another aspect, the invention features a chromatography column including a tubular member having an inlet and outlet end and first and second porous members disposed within the tubular member. A chromatography or separating media is disposed within the tubular member and bounded by the first and second porous members. The second porous member abuts the media and is held firmly by crimping a portion of the tubular member against the second porous member or into a grooved region of the second porous member.
Embodiments of the invention may include one or more of the following. The first porous member can be in slidable contact with an inner surface of the tubular member, and spaced sufficiently from the inlet end to form a module receiving region. The module receiving region is deep enough for a sample module to be inserted completely into the receiving region.
In another embodiment, the tubular member can be crimped near the inlet end and above the first porous member, such that the first porous member is restrained from sliding above the crimped portion of the tubular member. The crimped portion of the tubular member can be spaced sufficiently from the inlet end to form a module receiving region deep enough for a sample module to be inserted into the receiving region. Alternatively, the first porous member can be held firmly by crimping the tubular member against the porous member or into a grooved region of the first porous member. The crimped first porous member can be spaced sufficiently from the inlet end to form a module receiving region deep enough for a sample module to be inserted completely into the receiving region.
The tubular member can further include a sealing region between the inlet end and the module receiving region, the sealing region being sufficiently long to receive a sealing head for making a seal with the inner surface of the tubular member. The tubular member can further include a chamfered region near the inlet end.
In general, in another aspect, the invention features a chromatography column including a tubular member having an inlet end and an outlet end and first and second porous members disposed within the tubular member and in slidable contact with an inner surface of the tubular member. A chromatography or separating media is disposed within the tubular member and bounded by the first and second porous members. The tubular member is first crimped near the inlet end above the first porous member, such that the first porous member is restrained from sliding above the first crimping. The tubular member is also crimped near the outlet end below the second porous member, such that the second porous member is restrained from sliding below the second crimping. In one embodiment, the first crimping of the tubular member is spaced sufficiently from the inlet end to form a module receiving region deep enough for a sample module to be inserted into the receiving region.
The invention can be implemented to realize one or more of the following advantages. Using two or more layers of materials to form a composite column, the mechanical characteristics of the outer layer, and optionally intermediate layers, can provide structural benefits, such as rigidity, flexibility, deformability and hoop strength, while the properties of the inner layer, such as chemical inertness, can improve chromatographic performance. For example, a composite column having an outer layer formed from polypropylene or polyethylene, and an inner layer formed from a fluoropolymer, is cost-effective and able to achieve high levels of chromatographic performance relative to theoretical maximums, while achieving the necessary structural characteristics.
An inner layer formed from a fluoropolymer increases performance of the chromatography column, because, for example, the fluoropolymer does not interact with a solvent or compound being purified. Due to the higher performance, more concentrated fractions of purified components can be achieved, hence decreasing solvent consumption during the chromatography process.
The physical aspects of the column wall may be determined by the materials used in the outer or intermediate layers of the column wall. Flexible column walls may be used in a pressure vessel to radially compress the column and the chromatographic media within, thereby improving column performance. The combination of the outer, inner, and any intermediate layers may be chosen so that the column wall is deformable, so that it may be crimped, in order to fix a porous member in place, for example. The material for the outer layer may be chosen for its ability to be engraved, embossed, written upon, or otherwise inscribed. The thickness and cross-sectional shape of intermediate layers or the outer layer may be selected for particular physical characteristics, such as strength, flexibility, and durability. The cross-sectional shape of the outer layer may be selected for improved packaging and storage. For example, the cross-sectional shape of the outer layer may be selected to increase the number of columns that can be packed into a minimum space during use or storage. The cross-sectional shape of the outer layer may also be selected in order to include flat surfaces, protrusions, oblong surface(s), or other shapes that will prevent the column from rolling.
Use of beveled or chamfered edges at the inlet end of a composite chromatography column eases insertion of a scaling device, precolumn or sample module into the column. Additionally, beveled or chamfered edges can be advantageous in the manufacturing process, particularly if the composite columns are formed from molding.
The details of one or more embodiments of the invention are set forth in the accompanying drawings and the description below. Other features and advantages of the invention will be apparent from the description, the drawings, and the claims.